We are investigating the molecular mechanism of action of the suppressor-of-sable [su(s)] system of Drosophila melanogaster. Recessive su(s) mutations suppress recessive second-site mutations that are caused by insertions of the mobile elements 412 and P in 5' transcribed but non-translated sequences. Current evidence suggests that this suppression is effected by some mechanism that increases the amount of pseudo-wild-type mRNA that is produced by splicing the mobile element sequences from the primary transcript. The cDNA contains an open reading frame that encodes a putative polypeptide of 1322 amino acids. Cellular fractionation studies have shown that the protein is primarily located in the nucleus. This protein Pas one region of similarity to the RNA Recognition Motif (RRM) that is found in many proteins that are involved in RNA processing and a second highly charged region of similarity to the human, Xenopus and Drosophila 70K U1 binding proteins and to the Drosophila suppressor of white-apricot and transformer proteins, all of which are known to be RNA binding proteins. Portions of the cloned 25 kb of DNA have been reintroduced by P element-mediated transformation and allow an identification of genetic function with messages produced by the region. A segment of DNA which encodes only the su(s) message rescues both the primary phenotype of suppression and a secondary phenotype of cold-sensitive male Sterility. Studies of genetic deletions indicate that males and females lacking the entire su(s)[coding sequence are both viable and fertile, albeit markedly below the viabilities and levels of fertility of wild-type flies].